The proposed research is directed toward two fundamental needs in the area of toxicological evaluation of biomaterials: 1) immediate need for the evaluation of candidate biomaterials, and 2) the need for the improvement and standardization of tests. Three major objectives are proposed. I. Primary Acute Toxicity Screening of Candidate Biomaterials: A battery of acute toxicity tests, including tissue culture, hemolysis, intradermal irritation, systemic toxicity and intramuscular implantation, directly on the materials and extracts of materials will be used to evaluate candidate on the materials and extracts of materials will be used to evaluate candidate materials. II. Development of Standard Reference Materials for Toxicity Tests: Materials or test substances will be developed to provide a range of standard toxic responses appropriate for the standardization of acute toxicity tests employed in the evaluation of biomaterials for the purpose of intra- and interlaboratory validation of toxicity ratings. III. Development of a Sensitive Osmotic Fragility Test for the Detection of Leachable Components of Biomaterials: The quantitative and qualitative changes in the fragility of erythrocytes exposed to toxicants (or extracts of materials) are pertinent to blood-materials interactions, the fragility response being mediated by primary cell membrane interactions. A fragility response in the erythrocyte system indicates toxicant (leachable) concentrations adequate to perturb membranes of all formed elements of the blood as well as osmatic tissues. The limits of sensitivity of the test will be determined and correlations with acute tests made.